Genome wide identification of promoter binding sites for H4K12ac in human sperm and its relevance for early embryonic development.
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Genome wide identification of promoter binding sites for H4K12ac in human sperm and its relevance for early embryonic development. / Paradowska, Agnieszka S; Miller, David; Spiess, Andrej-Nikolai; Vieweg, Markus; Cerna, Martina; Dvorakova-Hortova, Katerina; Bartkuhn, Marek; Schuppe, Hans-Christian; Weidner, Wolfgang; Steger, Klaus.
In: EPIGENETICS-US, Vol. 7, No. 9, 9, 2012, p. 1057-1070.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Genome wide identification of promoter binding sites for H4K12ac in human sperm and its relevance for early embryonic development.
AU - Paradowska, Agnieszka S
AU - Miller, David
AU - Spiess, Andrej-Nikolai
AU - Vieweg, Markus
AU - Cerna, Martina
AU - Dvorakova-Hortova, Katerina
AU - Bartkuhn, Marek
AU - Schuppe, Hans-Christian
AU - Weidner, Wolfgang
AU - Steger, Klaus
PY - 2012
Y1 - 2012
N2 - Sperm chromatin reveals two characteristic features in that protamines are the predominant nuclear proteins and remaining histones are highly acetylated. Histone H4 acetylated at lysine 12 (H4K12ac) is localized in the post-acrosomal region, while protamine-1 is present within the whole nucleus. Chromatin immunoprecipitation in combination with promoter array analysis allowed genome-wide identification of H4K12ac binding sites. Previously, we reported enrichment of H4K12ac at CTCF binding sites and promoters of genes involved in developmental processes. Here, we demonstrate that H4K12ac is enriched predominantly between ± 2 kb from the transcription start site. In addition, we identified developmentally relevant H4K12ac-associated promoters with high expression levels of their transcripts stored in mature sperm. The highest expressed mRNA codes for testis-specific PHD finger protein-7 (PHF7), suggesting an activating role of H4K12ac in the regulatory elements of this gene. H4K12ac-associated genes revealed a weak correlation with genes expressed at 4-cell stage human embryos, while 23 H4K12ac-associated genes were activated in 8-cell embryo and 39 in the blastocyst. Genes activated in 4-cell embryos are involved in gene expression, histone fold and DNA-dependent transcription, while genes expressed in the blastocyst were classified as involved in developmental processes. Immunofluorescence staining detected H4K12ac from the murine male pronucleus to early stages of embryogenesis. Aberrant histone acetylation within developmentally important gene promoters in infertile men may reflect insufficient sperm chromatin compaction, which may result in inappropriate transfer of epigenetic information to the oocyte.
AB - Sperm chromatin reveals two characteristic features in that protamines are the predominant nuclear proteins and remaining histones are highly acetylated. Histone H4 acetylated at lysine 12 (H4K12ac) is localized in the post-acrosomal region, while protamine-1 is present within the whole nucleus. Chromatin immunoprecipitation in combination with promoter array analysis allowed genome-wide identification of H4K12ac binding sites. Previously, we reported enrichment of H4K12ac at CTCF binding sites and promoters of genes involved in developmental processes. Here, we demonstrate that H4K12ac is enriched predominantly between ± 2 kb from the transcription start site. In addition, we identified developmentally relevant H4K12ac-associated promoters with high expression levels of their transcripts stored in mature sperm. The highest expressed mRNA codes for testis-specific PHD finger protein-7 (PHF7), suggesting an activating role of H4K12ac in the regulatory elements of this gene. H4K12ac-associated genes revealed a weak correlation with genes expressed at 4-cell stage human embryos, while 23 H4K12ac-associated genes were activated in 8-cell embryo and 39 in the blastocyst. Genes activated in 4-cell embryos are involved in gene expression, histone fold and DNA-dependent transcription, while genes expressed in the blastocyst were classified as involved in developmental processes. Immunofluorescence staining detected H4K12ac from the murine male pronucleus to early stages of embryogenesis. Aberrant histone acetylation within developmentally important gene promoters in infertile men may reflect insufficient sperm chromatin compaction, which may result in inappropriate transfer of epigenetic information to the oocyte.
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Mice
KW - Mice, Inbred C57BL
KW - Protein Processing, Post-Translational
KW - Binding Sites
KW - Gene Expression Regulation, Developmental
KW - Promoter Regions, Genetic
KW - Genome, Human
KW - RNA, Messenger/biosynthesis
KW - Membrane Proteins/genetics/metabolism
KW - Histones/metabolism
KW - Spermatozoa/metabolism
KW - Acetylation
KW - Blastocyst/metabolism
KW - Chromatin/genetics/metabolism
KW - Embryonic Development/genetics
KW - Epigenesis, Genetic
KW - Genes, Developmental
KW - Transcription Factors/genetics/metabolism
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Mice
KW - Mice, Inbred C57BL
KW - Protein Processing, Post-Translational
KW - Binding Sites
KW - Gene Expression Regulation, Developmental
KW - Promoter Regions, Genetic
KW - Genome, Human
KW - RNA, Messenger/biosynthesis
KW - Membrane Proteins/genetics/metabolism
KW - Histones/metabolism
KW - Spermatozoa/metabolism
KW - Acetylation
KW - Blastocyst/metabolism
KW - Chromatin/genetics/metabolism
KW - Embryonic Development/genetics
KW - Epigenesis, Genetic
KW - Genes, Developmental
KW - Transcription Factors/genetics/metabolism
M3 - SCORING: Journal article
VL - 7
SP - 1057
EP - 1070
JO - EPIGENETICS-US
JF - EPIGENETICS-US
SN - 1559-2294
IS - 9
M1 - 9
ER -
